Localization and cell association of C1q in Alzheimer's disease brain
Localization and cell association of C1q in Alzheimer's disease brain
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DOI：
10.1006/exnr.1996.0043
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发表时间：
1996-03-01
影响因子：
5.3
通讯作者：
Tenner, AJ
中科院分区：
文献类型：
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作者：
Afagh, A;Cummings, BJ;Tenner, AJ
已显示补体蛋白Clq与纤维状β-淀粉样蛋白结合，导致经典补体途径的激活。Clq还被发现与脑中的大多数但不是全部淀粉样蛋白沉积有关。为了确定Clq是否仅与含有纤维状形式的β-淀粉样蛋白的斑块相关，使用硫代黄素和亲和纯化的抗人Clq抗体对正常和阿尔茨海默病脑进行化学双标记，硫代黄素特异性染色β-折叠构象的β-淀粉样蛋白。Clq免疫染色与几乎所有硫代黄酮阳性斑块共存，而在硫代黄酮阴性的β淀粉样蛋白免疫阳性斑块中未检测到Clq。非痴呆对照（其通常为噻托溴铵阴性）中的β-淀粉样蛋白斑也为Clq阴性。小胶质细胞和星形胶质细胞的反应形态也与Clq阳性斑块和神经元。有趣的是，AD脑中的许多神经元细胞，但不是小胶质细胞或星形胶质细胞，显着与抗C1 q染色。对照组神经元Clq不表达。我们的数据表明，这些Clq阳性结构中的一些神经元缠结免疫反应过度磷酸化的tau，这可能是结合细胞外Clq。然而，大量的C1 q阳性神经元具有完整的细胞形态，表明这些细胞可能正在合成这种关键的补体成分，因为C1 q的存在表明补体的激活和/或促炎事件的激活，并且含有C1 q的特定种类的斑块是对应于观察到的临床痴呆的类型，这些发现进一步支持补体在AD发病机制中起作用的假设。(C)出版社：Academic Press，Inc.
The complement protein, Clq, has been shown to bind to fibrillar beta-amyloid, resulting in the activation of the classical complement pathway. Clq has also been found associated with most but not all amyloid deposits in brain. To determine whether Clq is exclusively associated with plaques containing the fibrillar form of beta-amyloid, normal and Alzheimer brain were immunohistochemically double labeled using thioflavine, which specifically stains beta-amyloid in a beta-sheet conformation, and an affinity-purified antibody to human Clq. Clq immunostaining was colocalized with nearly all thioflavine-positive plaques, while Clq was not detected in beta-amyloid immunopositive plaques which were thioflavine-negative. beta-amyloid plaques in nondemented controls (which are typically thioflavine-negative) were also negative for Clq. Microglia and astrocytes of reactive morphology were also associated with Clq-positive plaques and neurons. Interestingly, many neuronal cells in the AD brain, but not microglia or astrocytes, stained prominently with anti-C1q. Neurons in control brain were not Clq positive. Our data suggest that some of these Clq-positive structures were neurofibrillary tangles immunoreactive for hyperphosphorylated tau, which may be binding extracellular Clq. However, a large number of the C1q-positive neurons had intact cell morphology, suggesting that these cells may be synthesizing this critical complement component, Since the presence of Clq suggests the activation of complement and/or the activation of proinflammatory events, and the specific class of plaques that contain Clq are the type that corresponds to observed clinical dementia, these findings further support the hypothesis that complement plays a role in the pathogenesis of AD. (C) 1996 Academic Press, Inc.